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Grb2 holds powerful molecular signaling pathway in check
Date:6/22/2012

HOUSTON - Once considered merely a passive link between proteins that matter, Grb2 - pronounced "grab2" - actually lives up to its nickname with its controlling grip on an important cell signaling pathway, scientists at The University of Texas MD Anderson Cancer Center report in the June 22 issue of Cell.

"Grb2 is a switch that controls normal signaling through the fibroblast growth factor receptor (FGFR)," said the paper's senior author, John Ladbury, Ph.D., professor in MD Anderson's Department of Biochemistry and Molecular Biology.

"Perhaps the best way to think about it is that Grb2 controls cell homeostasis (stable state) before a growth factor binds to FGFR, activating this molecular pathway," Ladbury said.

In addition to discovering a fundamental aspect of FGFR signaling, the researchers' discovery points to a potential explanation of why genomic alterations found in breast, bladder and gastric cancers and melanoma might promote cancer formation and growth, Ladbury noted.

FGFR has a docking station to receive growth factors on the cell surface, and another internal region that passes the growth factor signal on to proteins inside the cell by attaching phosphate groups to them.

FGFR employs phosphorylation to regulate a number of important processes, including the cell cycle, cell proliferation and migration. When some of these pathways become overactive, they can contribute to cancer growth and survival.

Like "a car idling in neutral" ready to go

Grb2's full name reflects its location: growth factor receptor-bound protein 2. In the great rush of molecular signaling pathway mapping in the 1990s, Ladbury noted that Grb2 was labeled an "adaptor protein," one that has no activity of its own apart from connecting to other proteins.

Mapping ran way ahead of figuring out each protein's function in a signaling pathway, Ladbury said, and scientists are still catching
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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